Phasic/tonic glial GABA differentially transduce for olfactory adaptation and neuronal aging

Neuron, Journal Year: 2024, Volume and Issue: 112(9), P. 1473 - 1486.e6

Published: March 5, 2024

Language: Английский

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Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 26(10), P. 5557 - 5567

Published: Aug. 12, 2021

In Alzheimer's disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation cognition-relevant gamma oscillations. The rhythm relies on proper neuronal spike-gamma coupling, specifically fast-spiking interneurons (FSN). Here we tested hypothesis that decrease in power and FSN synchrony precede amyloid plaque deposition cognitive impairment AppNL-G-F knock-in mice (AppNL-G-F). aim study was to evaluate amyloidogenic pathology progression novel mouse model using vitro electrophysiological network analysis. Using patch clamp FSNs pyramidal cells (PCs) simultaneous oscillation recordings, compared activity hippocampal wild-type (WT) at four stages (1, 2, 4, 6 months age). We found a severe is independent of, precedes Aβ formation, reported previously this animal model. increased Aβ1-42 concentration brain. Analysis cellular level showed an impaired coupling from 2 age From PC firing becomes desynchronized also, correlating reports literature robust mice. This provides evidence one earliest functional caused by likely main cause for oscillations consequent impairment. Our data suggests therapeutic approaches should be aimed restoring normal not just removal Aβ.

Language: Английский

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Intake of flavonoids from Astragalus membranaceus ameliorated brain impairment in diabetic mice via modulating brain-gut axis

Chinese Medicine, Journal Year: 2022, Volume and Issue: 17(1)

Published: Feb. 12, 2022

Abstract Background Brain impairment is one of a major complication diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus herbal medicine commonly used relieve the complications Flavonoids ingredients membranaceus, but its function and mechanism on diabetic encepholopathy still unknown. Methods Type 2 diabetes mellitus (T2DM) model was induced by high fat diet STZ in C57BL/6J mice, BEnd.3 HT22 cell lines were applied vitro study. Quality evaluated LC–MS/MS. Differential expressed proteins hippocampus proteomics; influence composition gut microbiota analyzed metagenomics. Mechanism Q-PCR, Western Blot, multi-immunological methods et al. Results We found that from (TFA) significantly ameliorated damage modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose food intake, repaired barrier, protected synaptic function; improved mitochondrial biosynthesis energy metabolism; enriched intestinal microbiome diet/STZ-induced mice. In study, we increased viability cells preserved barrier integrity CaCO monocellular layer, PGC1α/AMPK pathway participated this process. Conclusion Our findings demonstrated impairment, modulation gut-brain axis plays pivotal role. present study provided an alternative solution preventing treating cognition impairment.

Language: Английский

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Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease

npj Genomic Medicine, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 8, 2022

MicroRNAs (miRNAs) are found in nerve terminals, synaptic vesicles, and synaptosomes, but it is unclear whether cytosolic miRNA populations differ Alzheimer's disease (AD) or if synaptosomal miRNAs affect AD synapse activity. To address these questions, we generated synaptosomes fractions from postmortem brains of unaffected control (UC) samples analyzed them using a global Affymetrix microarray platform. A group significantly differed (P < 0.0001) with high fold changes variance (+/- >200-fold) their expressions different comparisons: (1) UC synaptosome vs cytosol, (2) (3) cytosol (4) synaptosomes. MiRNAs data analysis revealed that some potential were consistently across sample groups. These differentially expressed further validated brains, APP transgenic (Tg2576), Tau (P301L), wild-type mice. The miR-501-3p, miR-502-3p, miR-877-5p identified as upregulated progression based on Braak stages. Gene Ontology Enrichment Ingenuity Pathway Analysis showed the involvement nervous system development, cell junction organization, assembly formation, function GABAergic synapse. This first description versus significance function.

Language: Английский

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Somatostatin and the pathophysiology of Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102270 - 102270

Published: March 13, 2024

Language: Английский

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Biophysical models applied to dementia patients reveal links between geographical origin, gender, disease duration, and loss of neural inhibition

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: April 11, 2024

Abstract Background The hypothesis of decreased neural inhibition in dementia has been sparsely studied functional magnetic resonance imaging (fMRI) data across patients with different subtypes, and the role social demographic heterogeneities on this remains to be addressed. Methods We inferred regional by fitting a biophysical whole-brain model (dynamic mean field realistic inter-areal connectivity) fMRI from 414 participants, including Alzheimer’s disease, behavioral variant frontotemporal dementia, controls. then investigated effect disease condition, clinical variables local inhibitory feedback, variable related maintenance balanced excitation/inhibition. Results Decreased feedback was modeling results patients, specific brain areas presenting neurodegeneration. This loss correlated positively years showed differences regarding gender geographical origin patients. correctly reproduced known disease-related changes connectivity. Conclusions suggest critical link between abnormal circuit-level excitability levels, grey matter observed reorganization connectivity, while highlighting sensitivity underlying mechanism patient population.

Language: Английский

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A comprehensive review on the prevention and regulation of Alzheimer’s disease by tea and its active ingredients

Critical Reviews in Food Science and Nutrition, Journal Year: 2022, Volume and Issue: 63(30), P. 10560 - 10584

Published: June 1, 2022

Alzheimer's disease (AD) has brought a heavy burden to society as representative neurodegenerative disease. The etiology of AD combines multiple factors, concluding family, gender, head trauma, diseases and social psychology. There are hypotheses explaining the pathogenesis such β-amyloid (Aβ) deposition tau hyperphosphorylation, which lead extracellular amyloid plaques neurofibrillary tangles in neurons. existing therapeutic drugs have several disadvantages including single target, poor curative effect, obvious side effects. Tea contains many bioactive components, tea polyphenols (TPP), L-theanine (L-TH), pigment, polysaccharides caffeine. epidemiological investigations shown that drinking can reduce risk AD. mechanisms active ingredients prevention regulation includes reducing generation aggregation Aβ; inhibiting hyperphosphorylation; neuronal apoptosis regulate neurotransmitters; relieving oxidative stress neuroinflammation well intestinal flora. This review summarizes different signaling pathways Furthermore, we propose main limitations current research future directions, hoping contribute development natural functional foods based on treatment

Language: Английский

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NLRP3–GABA signaling pathway contributes to the pathogenesis of impulsive-like behaviors and cognitive deficits in aged mice

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: July 11, 2023

Abstract Background Perioperative neurocognitive disorders (PND), such as delirium and cognitive impairment, are commonly encountered complications in aged patients. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is aberrantly synthesized from reactive astrocytes following inflammatory stimulation implicated the pathophysiology of neurodegenerative diseases. Additionally, activation NOD-like receptor protein 3 (NLRP3) inflammasome involved PND. Herein, we aimed to investigate whether NLRP3–GABA signaling pathway contributes pathogenesis aging mice’s Methods 24-month-old C57BL/6 astrocyte-specific NLRP3 knockout male mice were used establish a PND model via tibial fracture surgery. monoamine oxidase-B (MAOB) inhibitor selegiline (1 mg/kg) was intraperitoneally administered once day for 7 days after PND, including impulsive-like behaviors evaluated by open field test, elevated plus maze, fear conditioning. Thereafter, pathological changes neurodegeneration explored western blot immunofluorescence assays. Results Selegiline administration significantly ameliorated TF-induced reduced excessive GABA production hippocampal astrocytes. Moreover, reversed impairment behaviors, decreased levels astrocytes, NLRP3-associated responses during early stage, restored neuronal degeneration hippocampus. Conclusions Our findings suggest that anesthesia surgical procedures trigger neuroinflammation deficits, which may be due hippocampus mice.

Language: Английский

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Comprehensive Review of Nutraceuticals against Cognitive Decline Associated with Alzheimer’s Disease

ACS Omega, Journal Year: 2023, Volume and Issue: 8(39), P. 35499 - 35522

Published: Sept. 20, 2023

Nowadays, nutraceuticals are being incorporated into functional foods or used as supplements with nonpharmacological approaches in the prevention and management of several illnesses, including age-related conditions chronic neurodegenerative diseases. Nutraceuticals apt for preventing treating such disorders because their nontoxic, non-habit-forming, efficient bioactivities promoting neurological well-being due to ability influence cellular processes neurogenesis, synaptogenesis, synaptic transmission, neuro-inflammation, oxidative stress, cell death modulation, neuronal survival. The capacity modify all these reveals potential develop food-based strategies aid brain development enhance function, prevent ameliorate neurodegeneration, possibly reverse cognitive impairment observed Alzheimer's disease, most predominant form dementia elderly. current review summarizes experimental evidence neuroprotective against describing mechanisms action vitro vivo models applied evaluate potential.

Language: Английский

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An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for pathogenesis Aβ affect balance in chemical neurotransmitters brain. Thus, current review examined role discusses alterations neurochemical activity cross talk with their receptors transporters. In presence tangles, changes may occur expression neuronal which turn triggers excessive release glutamate into synaptic cleft contributing to cell death damage. GABAergic system also be affected by AD pathology similar way. addition, decreased cholinergic dysfunction dopamine neurotransmission contribute damage cognitive function. Moreover, deficiencies noradrenergic neurons within locus coeruleus suggests that stimulation could useful addressing its pathophysiology. regulation melatonin, known effectiveness enhancing function preventing accumulation, along involvement serotonergic histaminergic cognition memory, becomes remarkable promoting AD. Additionally, nitric oxide adenosine-based therapeutic approaches play protective neuroinflammation. Overall, neurotransmitter-based strategies emerge as pivotal neurotransmitter homeostasis context This discussed potential drugs effective slowing correcting processes targeting imbalance Therefore, serve future strategy tackle

Language: Английский

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